Ion trap mass spectrometers, or quadrupole ion stores, have been known for many years and described by several authors. They are devices in which ions are formed and contained within a physical structure by means of electrostatic fields such as r.f., DC and a combination thereof. In general, a quadrupole electric field provides an ion storage region by the use of a hyperbolic electrode structure or a spherical electrode structure which provides an equivalent quadrupole trapping field.
The storage of ions in an ion trap is achieved by operating trap electrodes with values of r.f. voltage V and associated frequency f, DC voltage U, and device size r.sub.0 and z.sub.0 such that ions having mass-to-charge ratios within a finite range are stably trapped inside the device. The aforementioned parameters are sometimes referred to as trapping parameters and from these one can determine the range of mass-to-charge ratios that will permit stable trajectories and the trapping of ions. For stably trapped ions the component of ion motion along the axis of the trap may be described as an oscillation containing innumerable frequency components, the first component (or secular frequency) being the most important and of the lowest frequency, and each higher frequency component contributing less than its predecessor. For a given set of trapping parameters, trapped ions of a particular mass-to-charge ratio will oscillate with a distinct secular frequency that can be determined from the trapping parameters by calculation. In an early method for the detection of trapped ions, these secular frequencies were determined by a frequency-tuned circuit which coupled to the oscillating motion of the ions within the trap and allowed the determination of the mass-to-charge ratio of the trapped ions (from the known relationship between the trapping parameters, the frequency, and the m/z) and also the relative ion abundances (from the intensity of the signal).
Although quadrupole ion traps were first used as mass spectrometers over thirty years ago, the devices had not gained wide use until recently because the early methods of mass analysis were insufficient, difficult to implement, and yielded poor mass resolution and limited mass range. A new method of ion trap operation, the "mass-selective instability mode" (described in U.S. Pat. No. 4,540,884), provided the first practical method of mass analysis with an ion trap and resulted in the wide acceptance and general use of ion trap mass spectrometers for routine chemical analysis. In this method of operation, which was used in the first commercially-available ion trap mass spectrometers, a mass spectrum is recorded by scanning the r.f. voltage applied to the ring electrode whereby ions of successively increasing m/z are caused to adopt unstable trajectories and to exit the ion trap where they are detected by an externally mounted detector. The presence of a light buffer gas such as helium at a pressure of approximately 1.3.times.10.sup.-1 Pa was also shown to enhance sensitivity and resolution in this mode of operation.
The capabilities of quadrupole ion traps have continued to expand since the development of the mass-selective instability modes of operation described above. The versatility of these relatively simple mass spectrometers has been demonstrated by their high sensitivity in both electron and chemical ionization and their ability to serve as gas-phase ion/molecule reactors. The successful introduction of externally produced ions into these devices has even allowed the study of biomolecules using such techniques as laser desorption, cesium ion desorption, and electrospray ionization. The ion storage ability of the quadrupole ion trap makes possible tandem mass spectrometry (MS/MS) (U.S. Pat. No. 4,736,101) involving many stages of mass analysis with efficient dissociation of ions. Even parent MS/MS scans have been reported. The usable mass range of these mass spectrometers has been extended to 45,000 daltons (for singly charged ions) and beyond.
Although the mass-selective instability of operation was successful, a newer method of operation, the "mass-selective instability mode with resonance ejection" (described in U.S. Pat. No. 4,736,101) proved to have certain advantages such as the ability to record mass spectra containing a greater range in abundances of the trapped ions. In this method of operation, a supplementary field is applied across the end cap electrodes and the magnitude of the r.f. field is scanned to bring ions of successively increasing m/z into resonance with the supplementary field whereby they are ejected and detected to provide a mass spectrum. Commercially-produced ion trap mass spectrometers based on this mode of operation have recently become available, and these instruments have been successfully applied to an even wider variety of problems in chemical analysis than their predecessors.
Most recently, the mass resolution of the ion trap mass spectrometer has been extended by an improvement of the mass-selective instability mode using resonance ejection. In the improved mode, the electrical field is scanned in such a way that ions are brought into resonance, ejected, and detected at a rate such that the time interval between the ejection of successive m/z values is at least 200 times the period of the resonance frequency. This technique has allowed the ion trap to be used to distinguish isobaric ions and to resolve or partially resolve peaks due to multiply charged ions of successive masses. Although the resonance ejection enhancement of the mass selective instability scan allows an increased mass range and mass resolution, artifact peaks are often present in such spectra because of ejection from sources other than resonance ejection at the applied frequency.
In the mass selective instability scan (without resonance ejection), the field within the trap is scanned in such a way that the trapped ions encounter a region of instability so that they are sequentially ejected. In the first commercial instruments, the RF field was scanned linearly with time (no DC field being used) and the ions were ejected as they crossed the boundary of the Mathieu stability diagram, FIG. 2, at a.sub.z =0 and q.sub.z =0.908. Under these conditions the ions become unstable at the boundary and oscillate at a frequency of one half the RF frequency (.beta..sub.z =1). When resonance ejection was introduced to commercial instruments, the RF field was scanned in a similar way but a supplementary AC voltage with a frequency of only slightly less than one half the RF frequency was applied across the trap's end cap electrodes. Ions were ejected as they crossed the beta line associated with the resonance frequency, a beta value only slightly less than 1. Because this beta value was so close to the frequency associated with the edge of the stability diagram, there was little possibility that ions could exist at beta values between the value associated with the resonance frequency and the edge of the stability diagram.
However, whenever a resonance frequency is used that is significantly lower than one half the RF frequency, the possibility exists that ions may be ejected at either the resonance point or at the edge of the stability diagram as the RF field is scanned. In particular, in the "extended mass range" operation of the trap, the resonance frequency may be less than ten per cent of the value associated with a beta of 1, and a large range of q values exists between the q value associated with the resonance point and the q value of the edge of the stability diagram. This results in an occasional peak appearing at a place in the spectrum that is not expected from the calibration of the m/z scale (prepared from ions that are all ejected by resonance ejection). The m/z value of such an anomalous peak will therefore be assigned incorrectly.
In practice, these anomalous peaks occur with sufficient frequency to lead to considerable confusion in the assignment of mass scale. Many sources of anomalous peaks have been identified and encountered. The simplest cause of these anomalous peaks is applying the resonance ejection voltage at a time when ions are present with a q.sub.z between the edge of the stability diagram and the q.sub.z associated with the resonance ejection frequency. Also, occasionally only part of the ion population is ejected during the scan through the frequency of the resonance ejection voltage. The highest m/z resolution is attained with a lower ejection voltage, but a lower voltage also leads to a decreased ejection efficiency. Any ions that are not ejected remain in the trap until the RF voltage is increased to the point that the ions encounter the edge of the stability diagram. Ejection at the edge of the stability diagram is very efficient, and the mass spectrum will therefore show two different peaks arising from ions of the same m/z value. In such a case, we refer to the second peak (arising at the edge of the stability diagram) as a "ghost peak".
When using a trap of sufficiently distorted geometry (i.e., with an electric field sufficiently different from a pure quadrupole field), ejection may occur within the region of stability at well defined "non-linear resonance" lines, such as at .beta..sub.z =2/3 or .beta..sub.z +.beta..sub.r =1 (depending on the details of the geometric distortion). With such a trap, a ghost peak could arise from ions that survive resonance ejection, but are ejected as they cross the region of non-linear resonance, where ejection may occur without the application of a resonance voltage.
Anomalous peaks are frequently caused by ions created during the resonance ejection process. The resonance ejection scan is quite similar to the method used to fragment ions within the trap to obtain a ms/ms spectrum. Thus, fragment ions are sometimes created as the ions being ejected collide with the buffer gas. These daughter ions usually have m/z values less than that of the parent ion so that they are created with q.sub.z values between the value associated with the resonance ejection voltage and the q.sub.z value of the edge of the stability diagram. (Daughter ions of multiply-charged parent ions have even been observed with a m/z value of greater than the m/z of their parent, because of a loss of a charge during fragmentation. Such ions do not necessarily cause anomalous peaks because they are created with a q.sub.z of less than the value associated with the resonance ejection voltage.)
Anomalous peaks are also caused by ions created during the scan by processes other than dissociation during resonance ejection. Certain ions, especially multiply charged ions, spontaneously dissociate to product ions of lower m/z value. Chemical processes such as charge-exchange ionization may produce ions of lower m/z value. Other types of ion/molecule reactions are also frequently encountered in which ions are created that will be ejected at the edge of the stability diagram rather than at the q.sub.z associated with the resonance ejection voltage.
In a mass spectrum acquired using the mass selective instability mode with resonance ejection, those peaks arising from resonance ejection must be distinguished from those arising from ejection at the edge of the stability diagram, or at non-linear resonance lines, before the m/z value can be determined with complete confidence. We have discovered that the fine structure of the two different types of peaks may be used to distinguish them from one another.